This Program Project proposes a multidisciplinary approach to examine the function of several extracellular matrix (ECM) components of cartilage and bone by characterizing mice in which the genes for these components will have been disrupted by homologous recombination of embryonic stem cell. The program also proposes to use transgenic mice in order to study the mechanisms which control the tissue-specific expression of the genes for these components. Our goal is to capitalize on the strengths of the investigators, the complementary nature of the different projects and the powerful genetic approaches that are proposed to develop strongly interactive, collaborative projects. This program should help us gain considerable new knowledge about the mechanisms controlling the lineages and phenotypes of cells of skeletal tissues and about the function of individual cartilage and bone ECM components within larger multiprotein structures. These advances, which could not be effectively achieved by individual projects, should be very beneficial for our understanding of cartilage and bone diseases.